Antitumor effect of E7080 in oral carcinoma xenograft model

Abstract

Oral squamous cell carcinoma (OSCC) is difficult to treat, and advanced OSCC is particularly difficult as surgical treatment has an adverse effect on the patient’s quality of life. Current trials aim to identify a molecular target for managing OSCC to provide more selective treatment strategies. Angiogenesis and lymphangiogenesis are well-known mechanisms related to tumor growth and metastasis; hence, several studies focus on the identification of drugs that can inhibit angiogenesis and lymphangiogenesis in intra-tumoral or peritumoral areas. The purpose of this study was to evaluate the anti-tumor effect of E7080 in an OSCC nude mouse model by analyzing the tumor growth patterns. We evaluated the changes in CD31 and LYVE-1 expression in the tumor mass after oral administration of E7080. E7080 is a multiple tyrosine kinase inhibitor with anti-angiogenic and anti-lymphangiogenic effects. CD31 is an angiogenesis marker, whereas LYVE-1 is lymphangiogenesis marker. We measured staining densities by immunohistochemistry, using antibodies against CD31 and LYVE-1 to evaluate changes in angiogenesis and lymphangiogenesis, respectively, after oral administration of E7080 in a murine model of OSCC. Two human oral squamous cell lines, KB and SCC-9, were used in the study. Injection of OSCC tumor cells into the submandibular gland resulted in successful tumor growth in all animals. The treated groups showed higher body weights than the un-treated groups; the un-treated groups showed more rapid tumor growth than the treated groups in both SCC9 and KB subgroups; and the tumors were larger in the un-treated groups compared with those in the treated groups for both KB and SCC9 subgroups. Cervical lymph node metastasis was absent in the treatment group. Lung metastasis was absent in the treated KB subgroup, and the treated SCC9 subgroup showed one lung metastasis. The CD31 and LYVE-1 staining intensities were less in the E7080 treatment groups, but without statistical significance (P>0.05). In conclusion, OSCC tumor model is a reproducible method for cancer research, and E7080 is a potential candidate for the selective management of human OSCC.